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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:31:18 UTC
HMDB IDHMDB15058
Secondary Accession NumbersNone
Metabolite Identification
Common NameLevosimendan
DescriptionLevosimendan is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.
Structure
Thumb
Synonyms
ValueSource
LevosimendanumChEBI
SimdaxChEBI
LevosimedanHMDB
Chemical FormulaC14H12N6O
Average Molecular Weight280.2847
Monoisotopic Molecular Weight280.107259036
IUPAC Name1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide
Traditional Namelevosimendan
CAS Registry Number141505-33-1
SMILES
C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1
InChI Identifier
InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1
InChI KeyInChIKey=WHXMKTBCFHIYNQ-SECBINFHSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylhydrazines. These are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylhydrazines
Direct ParentPhenylhydrazines
Alternative Parents
Substituents
  • Phenylhydrazine
  • Pyridazinone
  • Pyridazine
  • Hydrazone
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Nitrile
  • Carbonitrile
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Anti-Arrhythmia Agents
  • Cardiotonic Agents
  • Phosphodiesterase Inhibitors
  • Vasodilator Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility8.81e-02 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.088 mg/mLALOGPS
logP2.69ALOGPS
logP2.16ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)10.53ChemAxon
pKa (Strongest Basic)4.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area113.43 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity77.63 m3·mol-1ChemAxon
Polarizability28.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00922
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00922
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00922
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2298414
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevosimendan
NuGOwiki LinkHMDB15058
Metagene LinkHMDB15058
METLIN IDNot Available
PubChem Compound3033825
PDB IDNot Available
ChEBI ID50567
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. [17323593 ]
  2. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M: Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. [17473298 ]
  3. MedicinesComplete [Link]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular weight:
124978.06
References
  1. Szilagyi S, Pollesello P, Levijoki J, Haikala H, Bak I, Tosaki A, Borbely A, Edes I, Papp Z: Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone. J Cardiovasc Pharmacol. 2005 Sep;46(3):369-76. [16116344 ]
General function:
Involved in inward rectifier potassium channel activity
Specific function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular weight:
43540.4
References
  1. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [17452812 ]
General function:
Involved in calcium ion binding
Specific function:
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
Gene Name:
TNNC1
Uniprot ID:
P63316
Molecular weight:
18402.4
References
  1. Kleerekoper Q, Putkey JA: Drug binding to cardiac troponin C. J Biol Chem. 1999 Aug 20;274(34):23932-9. [10446160 ]
  2. Levijoki J, Pollesello P, Kaivola J, Tilgmann C, Sorsa T, Annila A, Kilpelainen I, Haikala H: Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan. J Mol Cell Cardiol. 2000 Mar;32(3):479-91. [10731446 ]
  3. Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I: Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem. 2001 Mar 23;276(12):9337-43. Epub 2000 Dec 11. [11113122 ]
  4. Sorsa T, Pollesello P, Permi P, Drakenberg T, Kilpelainen I: Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides. J Mol Cell Cardiol. 2003 Sep;35(9):1055-61. [12967628 ]
  5. Lehmann A, Boldt J, Lang J, Isgro F, Blome M: [Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Sep;38(9):577-82. [12975736 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in inward rectifier potassium channel activity
Specific function:
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular weight:
47967.5
References
  1. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [17452812 ]